Peritoneal dialysate flow path sensing

ABSTRACT

The invention relates to systems and methods for sensing fluid characteristics of peritoneal dialysate infused into and removed from a patient during treatment. The systems and methods include sensors, processors, and flow paths for determining patient health based on the fluid characteristics of the peritoneal dialysate. The system can be a peritoneal dialysis cycler which can include an infusion line; an effluent line; at least one pump positioned in the infusion and/or effluent line; and at least one sensor fluidly connected to the effluent line. The sensor can be at least one of a flow sensor, an ion selective electrode, a pH sensor, a pressure sensor, a refractive index sensor, and a temperature sensor. The method can include infusing peritoneal dialysate through an infusion line; removing peritoneal dialysate through an effluent line; and determining at least one fluid characteristic of the peritoneal dialysate in the effluent line.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of and priority to U.S. patentapplication Ser. No. 15/666,614 filed Aug. 2, 2017, which claimspriority to Provisional Patent Application No. 62/373,133 filed Aug. 10,2016, the entire disclosures of each of which are incorporated byreference herein.

FIELD OF THE INVENTION

The invention relates to systems and methods for sensing fluidcharacteristics of peritoneal dialysate infused into and removed from apatient during treatment. The systems and methods include sensors,processors, and flow paths for determining patient health based on thefluid characteristics of the peritoneal dialysate.

BACKGROUND

Peritoneal Dialysis (PD) is a dialysis treatment that differs fromHemodialysis (HD) because blood is not removed from the body and passedthrough a dialyzer, but a catheter is placed in the peritoneal cavityand dialysate removed and introduced directly into the peritonealcavity. Blood is cleaned inside the patient using the patient's ownperitoneum as a type of dialysis membrane. The two primary classes of PDare Continuous Ambulatory Peritoneal Dialysis (CAPD) and ContinuousCycling Peritoneal Dialysis (CCPD) (or Automated Peritoneal Dialysis(APD)). In CAPD, dialysis is performed continuously by positioning a bagof peritoneal dialysate at shoulder level and using gravity to pull thefluid into the peritoneal cavity. The used dialysate is then drainedfrom the cavity and discarded. The time period that the dialysate is inthe cavity is called the dwell time and can range from 30 minutes to 4hours or more. CAPD is typically performed three, four or five times ina 24-hour period while a patient is awake. CAPD requires no cycler todeliver and remove the fluid.

Determination of specific fluid characteristics of the peritonealdialysate infused into and removed from the patient allows foroptimization of treatment and early medical intervention in the event ofworsening health. Known systems do not provide adequate mechanisms todetermine fluid characteristics of the dialysate used in peritonealdialysis during treatment. In particular, known systems do not allow theeffluent or filtrate removed from the patient to be sensed.

Hence, there is a need for systems and methods for determining fluidcharacteristics of the peritoneal dialysate. The need extends to systemsand methods monitoring the fluid characteristics during treatment. Thereis also a need for systems and methods to remove portions of theperitoneal dialysate over the course of treatment to determine anychanges to the peritoneal dialysate while in the peritoneal cavity ofthe patient.

SUMMARY OF THE INVENTION

The first aspect of the invention relates to a peritoneal dialysiscycler. In any embodiment, the peritoneal dialysis cycler can include acombined infusion and effluent line for delivering and receiving aperitoneal dialysate to and from a peritoneal cavity; at least one pumppositioned in the combined infusion and effluent line; and at least onesensor fluidly connected to the combined infusion and effluent line,wherein the at least one sensor is selected from the group of: a flowsensor, an ion selective electrode, a pH sensor, a pressure sensor, arefractive index sensor, and a temperature sensor. In any embodiment,the combined infusion and effluent line can be separated into twodifferent lines, which can be referred to as an infusion line and aneffluent line.

In any embodiment, the peritoneal dialysis cycler can include a samplingflow path fluidly connected to the combined infusion and effluent line,wherein the at least one sensor is positioned in the sampling flow path;a valve connecting the combined infusion and effluent line to thesampling flow path; and at least one pump in the sampling flow path.

In any embodiment, the peritoneal dialysis cycler can include adetachable sampling reservoir fluidly connected to the sampling flowpath.

In any embodiment, the peritoneal dialysis cycler can include aperitoneal dialysate generation flow path fluidly connected to thecombined infusion and effluent line; the peritoneal dialysate generationflow path having a water source; a water purification module; at leastone concentrate source fluidly connected to the peritoneal dialysategeneration flow path; and at least one sensor positioned in theperitoneal dialysate generation flow path or infusion line. If twoseparate infusion and effluent lines are used, the peritoneal dialysategeneration flow path can be fluidly connected to the infusion line.

In any embodiment, the peritoneal dialysis cycler can include adialysate regeneration module; the dialysate regeneration module fluidlyconnected to the combined infusion and effluent line and the peritonealdialysate generation flow path. If two separate infusion and effluentlines are used, the dialysate regeneration module can be fluidlyconnected to the effluent line.

In any embodiment, the dialysate regeneration module can be positioneddownstream of the sampling flow path.

In any embodiment, the peritoneal dialysis cycler can include aprocessor in communication with the at least one sensor; the processorreceiving data from the sensor and storing the data in amachine-readable storage medium.

In any embodiment, the processor can include an input/output interface,the input/output interface providing data from the at least one sensorto a user.

In any embodiment, the peritoneal dialysis cycler can include a samplingport fluidly connected to the combined infusion and effluent line. Iftwo separate infusion and effluent lines are used, the sampling portfluidly connected can be fluidly connected to the effluent line.

In any embodiment, the sampling port can be covered by a pierceableseptum.

The features disclosed as being part of the first aspect of theinvention can be in the first aspect of the invention, either alone orin combination.

The second aspect of the invention is drawn a method. In any embodiment,the method can include the steps of infusing peritoneal dialysate into apatient through a combined infusion and effluent line; and determiningat least one fluid characteristic of the peritoneal dialysate in theeffluent line. In any embodiment, the method can include the steps ofinfusing peritoneal dialysate into a patient through a separate infusionline; removing peritoneal dialysate from the patient through a separateeffluent line

In any embodiment, the method can include the step of pumping theperitoneal dialysate from the effluent line to a sampling reservoir;wherein the step of determining at least one fluid characteristic of theperitoneal dialysate includes determining the fluid characteristic inthe peritoneal dialysate in the sampling reservoir.

In any embodiment, the method can include the step of adding one or morereagents to the peritoneal dialysate in the sampling reservoir prior todetermining the fluid characteristic.

In any embodiment, the method can include the step of removing a portionof fluid from the combined infusion and effluent line through a samplingport, wherein the step of determining at least one fluid characteristicof the peritoneal dialysate includes determining the fluidcharacteristic in the removed fluid. If two separate infusion andeffluent lines are used, the step of removing a portion of fluid can beperformed using the effluent line.

In any embodiment, the method can include the step of determining atleast one fluid characteristic in the peritoneal dialysate in thecombined infusion and effluent line. If two separate infusion andeffluent lines are used, the step of determining at least one fluidcharacteristic in the peritoneal dialysate can be performed using theinfusion line.

In any embodiment, at least one fluid characteristic can be determinedin any one of the combined infusion and effluent line, the infusionline, and the effluent line.

In any embodiment, the fluid characteristic can be selected from thegroup of a pH of the fluid, and a volume of the fluid.

In any embodiment, the method can include the steps of a portion of theperitoneal dialysate from the patient through the effluent line at afirst time; removing a portion of the peritoneal dialysate from thepatient through the effluent at a second time; and determining the fluidcharacteristic at the first time and the second time.

In any embodiment, the fluid characteristic can be selected from thegroup of pH and concentration of one or more solutes.

In any embodiment, the method can include the step of communicating thefluid characteristic to a machine-readable storage medium in aprocessor.

The features disclosed as being part of the second aspect of theinvention can be in the second aspect of the invention, either alone orin combination.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic of a system for sensing fluid characteristics ofperitoneal dialysate in a flow path.

FIG. 2 is a schematic of a regenerative peritoneal dialysis system forsensing fluid characteristics of the peritoneal dialysate.

FIG. 3 is a flow chart illustrating a method of determining fluidcharacteristics in a sample of peritoneal dialysate.

DETAILED DESCRIPTION OF THE INVENTION

Unless defined otherwise, all technical and scientific terms usedgenerally have the same meaning as commonly understood by one ofordinary skill in the art.

The articles “a” and “an” are used to refer to one or to over one (i.e.,to at least one) of the grammatical object of the article. For example,“an element” means one element or over one element.

The term “combined infusion and effluent line” refers to a fluidconnector for delivering and removing fluid from a peritoneal cavity ofa patient. The combined infusion and effluent line can optionally beseparated into an independent infusion line and an independent effluentline.

The terms “communication” and “communicating” refer to an electronic orwireless link between two components.

The term “comprising” includes, but is not limited to, whatever followsthe word “comprising.” Use of the term indicates the listed elements arerequired or mandatory but that other elements are optional and can bepresent.

A “concentrate source” is a source of one or more solutes. Theconcentrate source can have one or more solutes with a soluteconcentration greater than the solute concentration to be used fordialysis. The concentrate in the concentrate source can also be lowerthan the solute concentration generally used in dialysis for generationof low concentration dialysate.

The terms “concentration” and “solute concentration” refers to an amountof a solute dissolved in a given amount of a solvent.

The term “conductivity sensor” refers to any component capable ofmeasuring the electrical conductance or the electrical resistance of afluid.

The term “consisting of” includes and is limited to whatever follows thephrase “consisting of.” The phrase indicates the limited elements arerequired or mandatory and that no other elements can be present.

The term “consisting essentially of includes whatever follows the term”consisting essentially of and additional elements, structures, acts orfeatures that do not affect the basic operation of the apparatus,structure or method.

The term “detachable” relates to any component of that can be separatedfrom a system, module, cartridge or any component of the invention.“Detachable” can also refer to a component that can be taken out of alarger system with minimal time or effort. In certain instances, thecomponents can be detached with minimal time or effort, but in otherinstances can require additional effort. The detached component can beoptionally reattached to the system, module, cartridge or othercomponent.

The terms “determining” and “determine” refer to ascertaining aparticular state of a system or variable(s).

The term “dialysate regeneration module” refers to a component orcomponents capable of removing waste products from a fluid.

The term “downstream” refers to a position of a first component in aflow path relative to a second component wherein fluid will pass by thesecond component prior to the first component during normal operation.The first component can be said to be “downstream” of the secondcomponent, while the second component is “upstream” of the firstcomponent.

The term “effluent line” refers to a fluid connector for removing fluidfrom a peritoneal cavity of a patient. The term “effluent line” can alsorefer to a combined effluent and infusion line.

The term “flow sensor” refers to any component capable of measuring avolume or a rate of fluid moving through a conduit.

A “fluid” is a liquid substance optionally having a combination of gasand liquid phases in the fluid. Notably, a liquid can therefore alsohave a mixture of gas and liquid phases of matter.

A “fluid characteristic” is any sensed characteristic of a fluid,including temperature, pressure, concentration, color, or any othercharacteristic.

The terms “fluidly connectable,” “fluidly connected,” “fluid connection”“fluidly connectable,” or “fluidly connected” refer to the ability topass fluid, gas, or mixtures thereof from one point to another point.The two points can be within or between any one or more of compartments,modules, systems, and components, all of any type.

The term “infusing” or to “infuse” a fluid refers to the movement ofperitoneal dialysate into the peritoneal cavity of a patient.

An “infusion line” is a fluid line for carrying peritoneal dialysateinto a body cavity or part of a patient such as a peritoneal cavity. Theterm “infusion line” can also refer to a combined effluent and infusionline.

The term “input/output interface” refers to a module of a processor orcomputing system that allows data to be received by the processor orcomputing system and provided by the processor or computing system. Theinput/output interfaces can automatically receive and provide data fromsensors, or can receive data manually input through the interface, suchas by a keyboard.

An “integrated cycler” is a component for movement of fluid into and outof the peritoneal cavity of a patient, wherein the integrated cyclerforms a part of an overall system. For example, the integrated cyclercan be contained in a housing with other components used for peritonealdialysis and be in fluid and electrical connection with desiredcomponents.

The term “ion selective electrode” refers to any component capable ofdetermining a concentration of a specific ion in a fluid based on adetected electrical potential.

The term “machine-readable storage medium” refers to any electronicdevice capable of storing information in a digital format for reading bya computer, processor, or other electronic device.

A “patient” or “subject” is a member of any animal species, preferably amammalian species, optionally a human. The subject can be an apparentlyhealthy individual, an individual suffering from a disease, or anindividual being treated for a disease.

“Peritoneal dialysate” is a dialysis solution to be used in peritonealdialysis having specified parameters for purity and sterility.Peritoneal dialysate is different than a dialysate used in hemodialysis,although peritoneal dialysate can be used in hemodialysis.

A “peritoneal dialysate generation flow path” is a path used ingenerating dialysate suitable for peritoneal dialysis.

“Peritoneal dialysis” is a therapy wherein a dialysate is infused intothe peritoneal cavity, which serves as a natural dialyzer. In general,waste components diffuse from a patient's bloodstream across aperitoneal membrane into the dialysis solution via a concentrationgradient. In general, excess fluid in the form of plasma water flowsfrom a patient's bloodstream across a peritoneal membrane into thedialysis solution via an osmotic gradient. Once the infused peritonealdialysis solution has captured sufficient amounts of the wastecomponents the fluid is removed. The cycle can be repeated for severalcycles each day or as needed.

The term “peritoneal dialysis cycler” or “cycler” refers to componentsfor movement of fluid into and out of the peritoneal cavity of apatient, with or without additional components for generating peritonealdialysate or performing additional functions.

The term “pH” refers to the hydrogen ion concentration in a fluid.

The term “pH sensor” refers to any component capable of measuring thehydrogen ion concentration in a fluid.

The term “pierceable septum” refers to a component through which aneedle or syringe can be inserted to draw fluid out of a flow path.

The term “portion of fluid” refers to an amount of a fluid less than theentire amount of the fluid in a flow path, container, or reservoir.

The term “positioned” refers to the location of a component.

The term “pressure sensor” refers to any component capable ofdetermining the force exerted by a fluid.

The term “processor” is a broad term and is to be given its ordinary andcustomary meaning to a person of ordinary skill in the art. The termrefers without limitation to a computer system, state machine, and/orprocessor designed to perform arithmetic or logic operations using logiccircuitry that responds to and processes the basic instructions thatdrive a computer. In any embodiment of the first, second, third, andfourth invention, the terms can include ROM (“read-only memory”) and/orRAM (“random-access memory”) associated therewith.

The term “pump” refers to any device that causes the movement of fluidsor gases by applying suction or pressure.

The terms “pumping,” “pumped,” or to “pump” refers to moving or flowinga fluid using a pump of any type known to those of ordinary skill in theart.

The term “reagent” refers to a substance that will react with a secondsubstance to produce an observable change in a solution.

The term “receiving” or to “receive” means to obtain information fromany source.

A “refractive index sensor” is any component capable of detecting theratio of the speed of light through a fluid to the speed of lightthrough water. The concentration of one or more solutes in the fluid canbe determined based on the refractive index.

The term “removing” fluid refers to flowing fluid out of a container,system, or patient.

The term “sampling flow path” refers to a flow path diverted from a mainflow path in which fluid characteristics of a fluid in the sampling flowpath can be determined.

The term “sampling port” refers to a fluid port in a flow path throughwhich a portion of the fluid in the flow path can be removed foranalysis.

The term “sampling reservoir” refers to a container for collecting aportion of a fluid for analysis of the fluid separate from the rest of asystem.

A “sensor” is a component capable of determining one or more states ofone or more variables in a system.

A “solute” is a substance dissolved in, or intended to be dissolved in,a solvent.

The term “storing” or to “store” refers to saving electronic data orinformation in a machine readable medium.

A “temperature sensor” is any component capable of measuring thetemperature of a fluid.

The term “transmitting” or to “transmit” refers to sending informationelectronically.

A “valve” is a device capable of directing the flow of fluid or gas byopening, closing or obstructing one or more pathways to allow the fluidor gas to travel in a path. One or more valves configured to accomplisha desired flow can be configured into a “valve assembly.”

The term “volume” refers to an amount of a fluid.

The term “water purification module” refers to a component or componentscapable of removing biological or chemical contaminants from water.

The term “water source” refers to a source from which potable water canbe obtained.

Peritoneal Dialysis Fluid Path Sensing

FIG. 1 illustrates a system 100 for sampling peritoneal dialysateremoved from a peritoneal cavity 10 of a patient. The system 100 caninclude a combined peritoneal dialysate effluent line and infusion line128, referred to herein as an effluent line, a peritoneal dialysategeneration flow path 104, at least one sensor 106-106 h, a peritonealdialysis cycler 116, and a computing device 120. The effluent line 128in the catheter has a single channel used for both filling and removalof effluent. One of skill in the art will understand that separateeffluent and infusion lines can be used. The system 100 can be embodiedan integrated cycler wherein the peritoneal dialysis cycler 116 includesthe peritoneal dialysate effluent line 128, the peritoneal dialysategeneration flow path 104, and the at least one sensor 106-106 h formingthe system 100 for sampling peritoneal dialysate removed from aperitoneal cavity 10. Alternatively, the peritoneal dialysis cycler 116can be nonintegrated without the peritoneal dialysate generation flowpath 104. Peritoneal dialysate can be prepared off-line and provided tothe cycler 116. The computing device 120 can be a part of the peritonealdialysis cycler 116, whether integrated or nonintegrated, or can beseparate device in communication with the sensors.

The peritoneal dialysate effluent line 128 can be fluidly connected to awaste reservoir (not shown) to collect effluent. Optionally, a samplingflow path 130 can be in fluid communication with the peritonealdialysate effluent line 102 for analysis of the fluid A valve (notshown) in the cycler can divert fluid from the effluent line 128 to thesampling flow path 130. The system 100 can divert a sample of effluentflowing through the peritoneal dialysate effluent line 102 to allowdetermination of fluid characteristics outside of the cycler 116. Thesample can be diverted continuously or at specific intervals and inpredetermined amounts. A valve (not shown) can be included toselectively divert peritoneal dialysate from the peritoneal dialysateeffluent line 102 into the sampling flow path 130. A pump (not shown)can provide an additional driving force for moving peritoneal dialysatethrough the sampling flow path 130. A similar analysis can be conductedon the generated peritoneal dialysate by diverting a volume of generatedperitoneal dialysate into the sampling flow path 130. Analysis of thegenerated peritoneal dialysate can serve as a quality check on the newlygenerated peritoneal dialysate, as well as calibration of the sensors bycomparing sensed values to known values of the dialysate. Analysis ofthe newly generated dialysate can also be used by the system forself-learning or machine learning to adjust the dialysate composition toa precision beyond the capabilities of known systems. Analysis of thegenerated peritoneal dialysate can also be used as a safety system toensure the concentration of solutes in the peritoneal dialysate iswithin a predetermined threshold of the expected values.

Alternatively or additionally, the system 100 can include a samplingport 134. The sampling port 134 can be fluidly connected to theperitoneal dialysate effluent line 102. The sampling port 134 canalternatively be fluidly connected to the sampling flow path 130. Thesampling port 134 can be covered by a pierceable septum. A user caninsert a needle or syringe through the pierceable septum to draw out aportion of the peritoneal dialysate in the effluent line 102 or samplingflow path 130. The pierceable septum can re-seal after removal of theneedle or syringe to avoid contamination of the peritoneal dialysate.

When used with an integrated cycler, the peritoneal dialysate generationflow path 104 can include a water source 108, one or more waterpurification modules 110, a concentrate source 112, a sterilizationmodule 114, and the peritoneal dialysis cycler 116. The concentratesource 112 can contain one or more solutes. The water source 108, waterpurification module 110, concentrate source 112, sterilization module114, and peritoneal dialysis cycler 116 can be fluidly connectable tothe peritoneal dialysate generation flow path 104. The peritonealdialysate generation flow path 104 can be fluidly connected to thecombined infusion and effluent line 128 to infuse peritoneal dialysateinto the peritoneal cavity 10. One of skill in the art will understandthat with a single concentrate source, solutes can be altered in thedialysate without changing the relative proportions of each solute. Withmultiple concentrate sources, each individual solute can be adjustedindependently of all other solutes. The concentration of the ioniccompounds in the ion concentrate source can also be lower than theconcentration generally used in dialysis for generation of lowconcentration dialysate. Any number of concentrate sources andconcentrate pumps can be used. A separate osmotic agent source and ionconcentrate source can be used to adjust the osmotic agent concentrationand other solute concentrations independently. Any solute usable inperitoneal dialysis can be included in the concentrate sources. Thewater source 108 can be a non-purified water source, such as tap water,wherein the water from the water source 108 can be purified by thesystem. A non-purified water source can provide water without additionalpurification, such as tap water from a municipal water source, waterthat has undergone some level of purification, but does not meet thedefinition of “purified water” provided, such as bottled water orfiltered water. The water source can contain water meeting the WHOdrinkable water standards provided in Guidelines for Drinking WaterQuality, World Health Organization, Geneva, Switzerland, 4th edition,2011. Alternatively, the water source 108 can be a source of purifiedwater, meaning water that meets the applicable standards for use inperitoneal dialysis without additional purification. The system pumpswater from the water source to a water purification module to removechemical contaminants in the fluid in preparation of the dialysate. Thewater purification module can be a sorbent cartridge containing anionand cation exchange resins and/or activated carbon. The system can pumpthe fluid to a sterilization module 114 for sterilizing the peritonealdialysate prior to infusion into the patient. The sterilization module114 can include one or more of a first ultrafilter, a secondultrafilter, and a UV light source, or any combination thereof. Thesterilization module can be any component or set of components capableof sterilizing the peritoneal dialysate.

The concentrate sources 112 can contain one or more solutes forgenerating the peritoneal dialysate from purified water. Theconcentrates in the concentrate source 112 are utilized to generate aperitoneal dialysis fluid that matches a dialysis prescription. Aconcentrate pump (not shown) in communication with the processor orcomputing unit controls the movement of fluid from the concentratesources 112 into the peritoneal dialysate generation flow path 104. Oneof skill in the art will understand that any number of concentratesources can be used, each containing concentrates of one or moresubstances. For example, the concentrate sources 112 can include anynumber of concentrates combined or in separate concentrate sources. Oneor more osmotic agent sources can be included in addition to a singleion concentrate source. Alternatively, multiple ion concentrate sourcescan be used with each ion concentrate in a separate concentrate source.Any combination of concentrates in any number of concentrate sources canbe used with the invention. The concentrate sources can infuse eachparticular concentrate to provide an infused ion concentration that islower than a prescribed amount for a particular patient. One desiredoutcome can be to provide a concentration for a particular ion that islower than a patient's pre-dialysis ion concentration. Additionally, ifmultiple ion sources are to be delivered by a concentrate source, thepresent system can selectively dilute a desired ion while maintainingconcentration levels for other ions. Hence, the present invention canavoid adjusting down every ion insofar as an added diluent may adverselyaffect concentrations of ions already in a normal range.

One or more fluid characteristics in the peritoneal dialysate removedfrom the patient can be determined by one or more sensors 106-106 h. Thesensors 106-106 h can be fluidly connected to one or more of theperitoneal dialysate effluent line 128, the sampling flow path 130, thesampling reservoir 132, and the peritoneal dialysate generation flowpath 104. For use with non-invasive sensors, the sensors 106 can bepositioned in the effluent line 128 and the sampling flow path 130 canbe optional. The sample can be tested while in the peritoneal dialysateeffluent line 128, the peritoneal dialysate generation flow path 104, orin the sampling flow path 130. Additionally or alternatively, a samplecan be diverted away from the peritoneal dialysate effluent line 102 andthen tested. For example, the sample can be diverted into the samplingflow path 130 fluidly connected to the peritoneal dialysate effluentline 102. The sample can be diverted through the sampling flow path 130into a detachable sampling reservoir 132 fluidly connected to thesampling flow path 130 for removal of the dialysate from the cycler 116and off-line testing. Certain fluid characteristics, such as color orclarity of the dialysate can require specialized equipment not includedin the effluent line 128, or the sampling flow path 130. The detachablesampling reservoir 132 allows a portion of the peritoneal dialysate tobe removed for determining any fluid characteristics with sensors notpresent in the effluent line 128 or sampling flow path 130. The samplecan be tested while in the sampling flow path 130 and/or the detachablesampling reservoir 132. Alternatively, the sample can be diverteddirectly to standalone system, such as a blood analyzer for analysis.Blood analyzers can determine several fluid characteristics, which canbe included in the system. One non-limiting example of a standaloneanalyzer is the Stat Profile® Critical Care Xpress analyzer by NovaBiomedical, however any analyzer can be used. The standalone analyzercan be in communication with the processor or computing unit of thesystem to provide the system with the results of the analysis.Specialized tubing with a T-junction or a valve can be used to divert avolume of fluid into the sampling flow path or to a standalone analyzer.In an embodiment, one or more sensors 106-106 h can be external to theperitoneal dialysis cycler 116 and the sample can be tested external tothe peritoneal dialysis cycler 116 in the sampling flow path 130. Thesystem an also include duplication of analysis with duplicated sensorsin multiple locations. For example, the same type of sensor can beincluded in both the effluent line 128 and in the sampling flow path130. Alternatively, a separate analyzer can be included for duplicationof analysis. Duplication of the analysis allows calibration of thesensors and acts as a safety check to ensure the sensors are properlyfunctioning. The duplicated sensors can be attached to the cycler 116 orin a standalone system.

The one or more sensors can be separate sensors or one or more combinedsensors. The one or more sensors 106-106 h can be in fluid communicationwith and positioned in or along one or more of the peritoneal dialysateeffluent line 128, the sampling flow path 130, the detachable samplingreservoir 132, and the peritoneal dialysate generation flow path 104.

Multiple instances of the one or more sensors 106-106 h are shown inFIG. 1. For example, a flow sensor 106 a can measure a volume ofperitoneal dialysate removed from a patient. A solute concentrationsensor 106 b can measure a solute concentration of the peritonealdialysate removed from the patient. The solute concentration sensor 106b can include a conductivity sensor or an ion selective electrode fordetermining the concentration of the ionic components of peritonealdialysate removed from the patient. A refractive index sensor 106 c canmeasure glucose or other osmotic agent concentration in the peritonealdialysate removed from the patient. A conductivity sensor 106 d canmeasure conductivity of the peritoneal dialysate removed from thepatient. A pressure sensor 106 e can measure a pressure of peritonealdialysate removed from the patient, and/or a pressure to infuseperitoneal dialysate into the patient, when included in infusion line104. A temperature sensor 106 f can measure a temperature of peritonealdialysate removed from the patient. A pH sensor 106 g can measure a pHlevel of peritoneal dialysate removed from the patient. An ion selectiveelectrode 106 h can measure the concentration of one or more specificsolutes in the peritoneal dialysate removed from the patient. Table 1provides non-limiting examples of sensors and methods that can determinesolute concentrations for a variety of solutes. Any one or more of thereagents in Table 1 can be added to the peritoneal dialysate todetermine a fluid characteristic. One of skill in the art willunderstand that alternative or additional methods can be used, and anysensor or method known in the art can be incorporated.

TABLE 1 Analyte Test Name Key Reagents Detection Total A280 NoneUV/Visible protein spectrophotometer @ 280 nm Total Coomassie (BradfordCoomassie Brilliant Blue UV/Visible protein Assay) G-250spectrophotometer @ 595 nm Total Bicinchoninic Acid Bicinchoninic acidUV/Visible protein (BCA, Smith Assay) Copper (II) sulfatespectrophotometer @ Lowry Assay 562 nm Total Pierce assay ProprietaryDye UV/Visible protein compounds spectrophotometer @ 660 nm CalciumO-cresolphthalein UV/Visible spectrophotometer @ 575 nm Calcium None Ionselective electrode Potassium None Ion selective electrode MagnesiumNone Ion selective electrode Glucose Glucose oxidase + Potentiometricplatinum electrode that reduces hydrogen peroxide to produce an electricsignal Glucose Glucose oxidase + UV/Visible peroxide reactive dyespectrophotometer @ (several available) dye specific wavelength

Referring to the tests listed in Table 1, UV/Vis spectrophotometry is anabsorption spectroscopy or reflectance spectroscopy technique thatoperates in the visible or ultraviolet spectral range. A UV/Visspectrophotometer exposes a chemical sample to light at predeterminedwavelength and measures either the absorption or reflection spectra thatis produced. The absorbance of the solution is proportional to theconcentration of the absorbing species and the path length, so theconcentration of the unknown sample can be quantified using acalibration curve developed using a series of samples of knownconcentration. Determination of protein concentration by measuringabsorbance at 280 nm (A280) is based on the absorbance of UV light bythe aromatic amino acids tryptophan and tyrosine, and by cystine,disulfide bonded cysteine residues, in protein solutions. Absorptioncorrelates with concentration, which can be quantified using acalibration curve developed with standards of known concentration. TheBradford (Coomassie) assay reacts Coomassie blue dye with protein in anacidic/methanol solution. The protein-dye complex has a blue color,whereas the unbound dye has a brown color. The amount of protein in thesolution can be quantified by measuring the intensity of the blue colorat 595 nm and comparing to a calibration curve developed with standardsof known concentration. The BCA (Smith) Assay primarily relies on tworeactions. First, the peptide bonds in protein reduce Cu²⁺ ions from thecopper(II) sulfate to Cu⁺ (a temperature dependent reaction). The amountof Cu²⁺ reduced is proportional to the amount of protein present in thesolution. Next, two molecules of bicinchoninic acid chelate with eachCu⁺ ion, forming a purple-colored complex that strongly absorbs light ata wavelength of 562 nm. Other commercially available protein assays havebeen developed to provide greater specificity and/or addressinterferences that can decrease utility of the assays described above.Many of the assays use proprietary dye molecules, but all use thegeneral procedure of preparing a protein-dye complex that results in acolor change that can be detected spectrophotometrically. Calcium ions(Ca2+) react with o-cresolphthalein complexone in an alkaline solutionto form an intense violet colored complex which maximally absorbs at 577nm. 2,3 8-Hydroxyquinoline can be added to remove interference bymagnesium and iron. In the method the absorbance of the Ca-oCPC complexis measured bichromatically at 570/660 nm. The resulting increase inabsorbance of the reaction mixture is directly proportional to thecalcium concentration in the sample. An ion-selective electrode (ISE) isa transducer (or sensor) that converts the activity of a specific iondissolved in a solution into an electrical potential. The voltage istheoretically dependent on the logarithm of the ionic activity,according to the Nernst equation. The ISE has a coating over theelectrodes that allow specific ions to interact with the electrodes, butreject other ions. Many types of ISE are commercially available withdifferent specificity and durability as needed for a specificapplication. ISE electrodes are available for calcium, magnesium,potassium and other ions of interest in PD fluid. Glucose can bequantified using a sensor that utilizes glucose oxidase. Glucose oxidaseis an enzyme that oxidizes glucose to D-glucono-1,5 lactone+hydrogenperoxide. The hydrogen peroxide that is produced can be reduced on aplatinum electrode to produce an electrical signal proportional toconcentration. Alternatively, the peroxide can be complexed with areactive dye, such as Amplex® Red reagent(10-acetyl-3,7-dihydroxyphenoxazine) to produce a colored complex thatcan be quantified using a UV/Vis spectrophotometer. Other peroxidereactive dyes are commercially available to measure peroxideconcentration.

The computing device 120 can include the one or more processors 122,memory 124, and one or more input/output interfaces 126. One of ordinaryskill in the art will recognize that the memory 124 can includelong-term memory and operating memory, and/or memory serving as bothlong-term memory and operating memory. The memory 124 can be amachine-readable storage medium. The memory 124 can be in communicationwith the processor 122 and store instructions that when executed performany of the methods of the present invention. The input/outputinterface(s) 126 can include an input port to receive information fromthe one or more sensors 106-106 h, and an output interface to outputdata to a user, such as a notification regarding the sample. Theprocessor 122 can be in communication with the at least one sensor106-106 h and store data received from the at least one sensor 106-106 hin the memory 124. As with all features of the present application,intervening components, such as the input/output interface 126, can bepresent between the processor 122 and the sensors 106-106 h. Thecomputing device 120 can be a stand-alone device independent of theperitoneal dialysis cycler 116, or can be a part of the peritonealdialysis cycler 116. The computing device 120 can be a remote device innetwork communication with the sensor(s) 106-106 h, such as via theInternet.

FIG. 2 shows an alternative system 200 for sampling peritoneal dialysateto determine one or more fluid characteristics of the dialysate removedfrom the patient. A difference between system 200 and system 100 is theprovision of a peritoneal dialysate regeneration module 210. Adiscussion of some features similar to the features of system 100 isomitted in the interest of brevity.

The peritoneal dialysis cycler 216 can include a pump 218, a combinedinfusion and effluent line 228, referred to herein as an effluent line,and a dialysate regeneration line 202. The effluent line 228 can befluidly connected to the peritoneal dialysate generation flow path 204downstream of the sterilization module 114. The peritoneal dialysateregeneration line 202 can be fluidly connected to the peritonealdialysate generation flow path 204 upstream of the peritoneal dialysateregeneration module 210. The peritoneal dialysate regeneration module210 can be positioned downstream of the optional sampling flow path 230.

Certain fluid characteristics require additional reagents or dyes fordetermination. In one non-limiting example, determination of glucoseconcentration requires that glucose react with glucose oxidase toproduce hydrogen peroxide. The hydrogen peroxide formed through thereaction together with 4 amino-antipyrene (4-AAP) and phenol in thepresence of peroxidase yield a red quinoeimine dye that can be measuredspectrophotometrically at 505 nm. Alternatively, the hydrogen peroxidecan be reacted with an appropriate electrode sensor that produceselectric current in proportion to glucose concentration. Similarly, theprotein content in peritoneal dialysate effluent can be detected by anysuitable protein bioassay. In one non-limiting example, CoomassieBrilliant Blue G-250 dye is reacted with protein to form a coloredcomplex that can be detected spectrophotometrically. The color intensitycorrelates with protein concentration. One of skill in the art willunderstand that alternative reagents can be used to determine the sameor different fluid characteristics. Many of the reagents cannot bepassed back to the patient when the peritoneal dialysate is regeneratedand reused. The sampling flow path 230 allows necessary reagents to beadded to the dialysate removed from the patient in a diverted flow path,ensuring that the reagents are not passed back into the dialysategeneration flow path 204 and to the patient. Sensors that do not requirethe addition of reagents can alternatively be present in the effluentline 128, and the sampling flow path 130 is optional. A detachablesampling reservoir can allow a portion of the peritoneal dialysateremoved from the patient to be analyzed off-line.

The system 200 can include a peritoneal dialysate effluent line 228, aperitoneal dialysate generation flow path 204, at least one sensor106-106 h, a peritoneal dialysis cycler 216, and a computing device 120as shown in FIG. 1.

The operation of the systems 100, 200 of FIGS. 1 and 2 is shown in FIG.3, which is a schematic representation of an exemplary computerizedmethod 300 for sampling peritoneal dialysate removed from a peritonealcavity 10 of a patient. In operation 302, the method 300 can start. Aperitoneal dialysis session can be initiating or already underway inoperation 302.

In operation 304, a control signal(s) initiating a cycle of theperitoneal dialysis session can be issued by the processor 122 of thesystem 100, 200 controlling components of peritoneal dialysategeneration flow path 104, 204. Peritoneal dialysate can be infused intothe peritoneal cavity 10 of a patient through the effluent line 128,228. The method can proceed to operation 306.

In operation 306, a control signal(s) ending the cycle of the peritonealdialysis session can be issued by the processor 122 of the system 100,200. The control signal can cause the peritoneal dialysis cycler 116,216 to initiate a drain portion of the cycle. Peritoneal dialysate canbe removed from the peritoneal cavity of the patient 10 through theperitoneal dialysate effluent line 128, 228. The method can proceed tooperation 308.

In operation 308, a control signal(s) diverting a sample of theperitoneal dialysate flowing through the peritoneal dialysate effluentline 128, 228 can be issued by the processor 122. Multiple instances ofoperation 308 are depicted in FIG. 3. For example, in operation 308 a,the control signal(s) can cause the sample to be removed from theperitoneal dialysate flowing through the peritoneal dialysate effluentline 128, 228 and into the sampling flow path 130, 230. In operation 308b, the control signal(s) can cause the sample to be removed from theperitoneal dialysate flowing through the peritoneal dialysate effluentline 128, 228 and into the detachable sampling reservoir 132. In anyembodiment, the sample can be pumped from the effluent line 128, 228,through a valve into the sampling flow path 130 and optionally to thedetachable sampling reservoir 132. Alternatively, the sample can bediverted from the peritoneal dialysate effluent line 128, 228 anddirectly into the detachable sampling reservoir 132 or a standaloneanalyzer. In operation 308 c, the peritoneal dialysate can be removedfrom the effluent line 128, 228 through a sampling port. For example, asyringe needle can be mechanically or manually inserted through thepierceable septum and a portion of the peritoneal dialysate can beremoved for off-line analysis. Alternatively, one or more of the sensorscan be positioned in the effluent line 128, 228, and the system need notdivert a portion of the effluent. The method 300 can proceed tooperation 310.

In operation 310, data can be received by the processor 122 from thesensors 106-106 h regarding the sample. For example, the one or moresensors in fluid communication with the sampling flow path 130 canreceive data representing a characteristic of the peritoneal dialysate.Alternatively, one or more sensors in the peritoneal dialysate effluentline 128, 228, the peritoneal dialysate generation flow path 104, 204,or a standalone analyzer, can receive data representing a characteristicof the peritoneal dialysate. Additionally or alternatively, the datareceived in operation 310 can be analyzed by the processor 122 todetermine the characteristic of the peritoneal dialysate in operation312. The data received from the sensors in operation 310 can be storedin a machine-readable storage medium. The method 300 can proceed tooperation 314, and the data received from the sensors can be transmittedto a user. As another example, the one or more sensors in fluidcommunication with the detachable fluid reservoir 132 can receive datarepresenting a characteristic of the peritoneal dialysate in theperitoneal dialysate effluent line 128, 228. As yet another example, oneor more sensors 106-106 h can output data from the sample after theperitoneal dialysate is removed using the sampling port 134. The step ofdetermining a characteristic of the peritoneal dialysate in operation312 can include determining the characteristic of the peritonealdialysate after the peritoneal dialysate is removed using the samplingport 134.

One of ordinary skill in the art will recognize that multiple fluidcharacteristics can be sampled by sensors 106-106 h of systems 100, 200of FIGS. 1 and 2. Table 2 contains non-limiting examples of sensors106-106 h and corresponding sampled characteristics of the peritonealdialysate.

TABLE 2 Sensor Fluid Characteristic Flow sensor Volume of fluidRefractive index sensor Osmotic agent concentration in fluidConductivity sensor Conductivity of fluid Pressure sensor Pressure todeliver/remove fluid Temperature sensor Temperature of fluid pH sensorpH of fluid Ion selective electrode Concentration of specific ions influid

Fluid characteristics of both the peritoneal dialysate in the infusionline being infused into the patient, and the peritoneal dialysate in theeffluent line can be determined. Determining the fluid characteristic inboth the infusion line and the effluent line allows for determinationsof changes to the peritoneal dialysate while inside the peritonealcavity of the patient during a dwell period. For example, the pH of theperitoneal dialysate infused into the patient and the pH of theperitoneal dialysate removed from the patient allows a determination ofthe change in pH during the dwell period. A drop in dialysate pH duringthe dwell period can indicate an infection in the patient, or poormembrane transfer efficiency. Flow sensors in both the infusion line andthe effluent line can be used to determine the volume of peritonealdialysate infused into the patient and the volume of peritonealdialysate removed from the patient. The difference between the volume ofperitoneal dialysate infused into the patient and removed from thepatient provides the net fluid removal, or ultrafiltration, from thepatient.

The system can divert peritoneal dialysate into the effluent line atmultiple times. A portion of the peritoneal dialysate in the peritonealcavity of the patient can be removed at a first time and a second time,allowing the changes in a fluid characteristic to be determined. Adecrease in the pH of the dialysate over time could indicate infectionor poor membrane transfer efficiency. Membrane transfer efficiency canalso be calculated by measuring changes in solute concentration of thedialysate at multiple times during the dwell period. Concentrations ofsolutes measured at multiple times during the dwell period can also beused to determine the optimal time to end a peritoneal dialysis cycle.For example, a plateau in the concentration of one or more solutes,including an osmotic agent concentration, could indicate thatequilibrium between the patient and the dialysate has been achieved, anda new cycle started.

One skilled in the art will understand that various combinations and/ormodifications and variations can be made in the systems and methodsdepending upon the specific needs for operation. Features illustrated ordescribed as being part of an aspect of the invention can be used in theaspect of the invention, either alone or in combination.

What is claimed is:
 1. A system, comprising: a peritoneal dialysiscycler having either an effluent line or a combined infusion andeffluent line; at least one solute concentration sensor in communicationwith the effluent line or combined infusion and effluent line; and aprocessor; the processor programmed to determine a concentration of atleast one solute in an effluent from a patient based on data from thesolute concentration sensor.
 2. The system of claim 1, the processorprogrammed to determine a change in concentration of the at least onesolute in a peritoneal dialysate during a dwell time based on data fromthe solute concentration sensor.
 3. The system of claim 1, wherein theat least one solute comprises an osmotic agent.
 4. The system of claim1, wherein the at least one solute comprises glucose or dextrose.
 5. Thesystem of claim 1, wherein the solute concentration sensor is arefractive index sensor.
 6. The system of claim 1, the processorprogrammed to determine a membrane transfer efficiency based on thechange in concentration of the at least one solute.
 7. The system ofclaim 1, the processor programmed to divert peritoneal dialysate from apatient to the at least one solute concentration sensor at multipletimes during a dwell period.
 8. The system of claim 1, wherein the atleast one solute concentration sensor is positioned in a sampling flowpath fluidly connected to the effluent line or combined infusion andeffluent line.
 9. The system of claim 8, further comprising a peritonealdialysate generation flow path fluidly connected to an infusion line orthe combined infusion and effluent line; the peritoneal dialysategeneration flow path comprising one or more concentrate sources and awater source; the peritoneal dialysate generation flow path fluidlyconnected to the sampling flow path.
 10. The system of claim 9, theprocessor programmed to determine a concentration of at least one solutein a generated peritoneal dialysate from the peritoneal dialysategeneration flow path.
 11. The system of claim 10, wherein the at leastone solute comprises an osmotic agent.
 12. The system of claim 10,wherein the at least one solute comprises glucose or dextrose.
 13. Thesystem of claim 10, wherein the processor is programmed to determine achange in concentration of the at least one solute based on theconcentration of the at least one solute in the generated peritonealdialysate and the concentration of the at least one solute in theeffluent from the patient.
 14. The system of claim 1, wherein the atleast one solute concentration sensor is positioned in a samplingreservoir fluidly connected to the effluent line or combined infusionand effluent line.
 15. The system of claim 14, further comprising aperitoneal dialysate generation flow path fluidly connected to aninfusion line or the combined infusion and effluent line; the peritonealdialysate generation flow path comprising one or more concentratesources and a water source; the peritoneal dialysate generation flowpath fluidly connected to the sampling reservoir.
 16. The system ofclaim 15, the processor programmed to determine a concentration of atleast one solute in a generated peritoneal dialysate from the peritonealdialysate generation flow path.
 17. The system of claim 16, wherein theat least one solute comprises an osmotic agent.
 18. The system of claim16, wherein the at least one solute comprises glucose or dextrose. 19.The system of claim 1, further comprising at least a second sensor incommunication with the effluent line or combined infusion and effluentline.
 20. The system of claim 19, wherein the second sensor is selectedfrom a group consisting of: an ion selective electrode, a pH sensor, apressure sensor, a refractive index sensor, and a temperature sensor.